This program performs basic research elucidating mechanisms of pain and analgesia, and develops improved methods of pain evaluation. Experimental and clinical findings have formed the basis for branch studies in experimental and clinical studies of neuropathic pain and in brain imaging. The program uses animal models and evaluates normal volunteers and selected patients at NIH, and collaborates with several investigators involved in clinical care of target patient populations. One section of the program focuses on primary afferent mechanisms. The program has developed a new animal model of nerve inflammation and a new clinical method to isolate pain sensations mediated either by thinly myelinated Ad afferents or the unmyelinated C-fiber afferents. An additional section evaluated mechanisms of analgesia, A study this year suggests that opioid Ad effects commonly observed in experiments with pain-free volunteers may not predict opioid C- fiber effects commonly observed in clinical conditions. These methods will continue to be improved and will be applied in basic and clinical studies of neuropathic pain. The program's main focus has been on spinal mechanisms that modulate pain input. We have identified neural mechanisms underlying neuropathic pain conditions and have used a human experimental model involving intradermal injections of capsaicin, the pungent ingredient in chili pepper. Recent results confirm that allodynia and hyperalgesia cross dermatomes, a symptom previously associated with a psychiatric diagnosis. The program collaborates with a number of NIH Institutes and external institutions. These include studies of mucosal pain with Maria Turner of NCI, studies of cardiac pain with Richard Cannon of NHLBI, studies of the mechanisms of orofacial pain with Kevin Reid now at the Mayo Clinic, studies of spinal temporal pain summation with Ole Andersen at Aalborg University, Denmark, and studies of patients with neuropathic pain in conjunction with Norman Harden at the Rehabilitation Institute of Chicago. A fourth program area, supraspinal mechanisms, is currently pursued in clinical studies with Fred Lenz in the department of Neurosurgery at Johns Hopkins University and will be pursued in new studies at NIH with Michael Iadarola and Dan Kenshalo that integrate studies of human brain imaging using fMRI and primate physiology and behavior.